Multitudes of messages - p1385

doi:10.1038/ng1208-1385

Tissue-specific expression of mRNA isoforms and interindividual differences in isoform usage can now be quantitated by genome-wide assays, both by custom microarray and by next-generation sequencing.

Abstract - | Full Text - Multitudes of messages | PDF (142 KB) - Multitudes of messages

Lack of support for association between common variation in TNFSF4 and myocardial infarction in a German population - pp1386 - 1387

Werner Koch, Petra Hoppmann, Jakob C Mueller, Albert Schömig & Adnan Kastrati

doi:10.1038/ng1208-1386

Full Text - Lack of support for association between common variation in TNFSF4 and myocardial infarction in a German population | PDF (129 KB) - Lack of support for association between common variation in TNFSF4 and myocardial infarction in a German population | Supplementary information

Reply to "Lack of support for association between common variation in TNFSF4 and myocardial infarction in a German population" - pp1387 - 1388

Xiaosong Wang, Massimiliano Ria, Per Eriksson, Ulf de Faire, Anders Hamsten & Beverly Paigen

doi:10.1038/ng1208-1387

Full Text - Reply to "Lack of support for association between common variation in TNFSF4 and myocardial infarction in a German population" | PDF (119 KB) - Reply to "Lack of support for association between common variation in TNFSF4 and myocardial infarction in a German population"

The genesis of genetics - p1389

Marga Vicedo reviews In Pursuit of the Gene: From Darwin to DNA by James Schwartz

doi:10.1038/ng1208-1389

Full Text - The genesis of genetics | PDF (143 KB) - The genesis of genetics

Cell cycle micromanagement in embryonic stem cells - pp1391 - 1392

V Narry Kim

doi:10.1038/ng1208-1391

Embryonic stem (ES) cells undergo rapid cell division without compromising their ability to differentiate into virtually all cell types. Using ES cells deficient for a microRNA biogenesis factor, Dgcr8, a new report uncovers the importance of specific microRNAs in the ES cell cycle transition from G1 to S phase.

Abstract - | Full Text - Cell cycle micromanagement in embryonic stem cells | PDF (180 KB) - Cell cycle micromanagement in embryonic stem cells

See also: Letter by Wang et al.

Phenotypic variations on the theme of CNVs - pp1392 - 1393

Michael C O'Donovan, George Kirov & Michael J Owen

doi:10.1038/ng1208-1392

Copy number variation has emerged as an important type of genetic risk factor for developmental disorders, including the neurodevelopmental disorders schizophrenia, autism and mental retardation. The highly pleiotropic effects observed for specific copy number variants (CNVs) challenge current classification of these disorders, but also provide opportunities to understand their origins and the relationships between them.

Abstract - | Full Text - Phenotypic variations on the theme of CNVs | PDF (203 KB) - Phenotypic variations on the theme of CNVs

See also: Letter by Brunetti-Pierri et al.

Nonsynonymous variants and fatty liver disease - pp1394 - 1395

Karen L Mohlke

doi:10.1038/ng1208-1394

Fat accumulation in the liver is a common trait that may progress to severe liver disease. A new study identifies common and rare nonsynonymous variants in PNPLA3 that are associated with hepatic triglyceride content and that may explain some of the population differences in prevalence.

Abstract - | Full Text - Nonsynonymous variants and fatty liver disease | PDF (174 KB) - Nonsynonymous variants and fatty liver disease

See also: Letter by Romeo et al.

Research highlights - p1397

Orli Bahcall, Lily Khidr, Emily Niemitz, Alan Packer & Kyle Vogan

doi:10.1038/ng1208-1397

Full Text - Research highlights | PDF (117 KB) - Research highlights

Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci - pp1399 - 1401

Jason D Cooper, Deborah J Smyth, Adam M Smiles, Vincent Plagnol, Neil M Walker, James E Allen, Kate Downes, Jeffrey C Barrett, Barry C Healy, Josyf C Mychaleckyj, James H Warram & John A Todd

doi:10.1038/ng.249

Jason Cooper and colleagues identify four new risk loci for type 1 diabetes through a meta-analysis of data from three genome-wide association studies, with replication in additional case-control and family-based samples, providing further insights into the genetic risk factors underlying this disease.

Abstract - | Full Text - Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci | PDF (175 KB) - Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci | Supplementary information

Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis - pp1402 - 1403

Yurii S Aulchenko, Ilse A Hoppenbrouwers, Sreeram V Ramagopalan, Linda Broer, Naghmeh Jafari, Jan Hillert, Jenny Link, Wangko Lundström, Eva Greiner, A Dessa Sadovnick, Dirk Goossens, Christine Van Broeckhoven, Jurgen Del-Favero, George C Ebers, Ben A Oostra, Cornelia M van Duijn & Rogier Q Hintzen

doi:10.1038/ng.251

Rogier Hintzen and colleagues report the results of a search for genetic variants associated with susceptibility to multiple sclerosis in a genetically isolated population that lead to identification of a new susceptibility locus in the region of the KIF1B gene on chromosome 1.

Abstract - | Full Text - Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis | PDF (240 KB) - Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis | Supplementary information

Lung cancer susceptibility locus at 5p15.33 - pp1404 - 1406

James D McKay, Rayjean J Hung, Valerie Gaborieau, Paolo Boffetta, Amelie Chabrier, Graham Byrnes, David Zaridze, Anush Mukeria, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, John McLaughlin, Frances Shepherd, Alexandre Montpetit, Steven Narod, Hans E Krokan, Frank Skorpen, Maiken Bratt Elvestad, Lars Vatten, Inger Njølstad, Tomas Axelsson, Chu Chen, Gary Goodman, Matt Barnett, Melissa M Loomis, Jan Lubiñski, Joanna Matyjasik, Marcin Lener, Dorota Oszutowska, John Field, Triantafillos Liloglou, George Xinarianos, Adrian Cassidy, EPIC Study, Diana Zelenika, Anne Boland, Marc Delepine, Mario Foglio, Doris Lechner, Fumihiko Matsuda, Helene Blanche, Ivo Gut, Simon Heath, Mark Lathrop & Paul Brennan

doi:10.1038/ng.254

Paul Brennan and colleagues report a genome-wide association study for lung cancer susceptibility. In addition to a previously reported variant at 15q25, they detect and replicate a new association at 5p15.33.

Abstract - | Full Text - Lung cancer susceptibility locus at 5p15.33 | PDF (235 KB) - Lung cancer susceptibility locus at 5p15.33 | Supplementary information

Common 5p15.33 and 6p21.33 variants influence lung cancer risk - pp1407 - 1409

Yufei Wang, Peter Broderick, Emily Webb, Xifeng Wu, Jayaram Vijayakrishnan, Athena Matakidou, Mobshra Qureshi, Qiong Dong, Xiangjun Gu, Wei Vivien Chen, Margaret R Spitz, Timothy Eisen, Christopher I Amos & Richard S Houlston

doi:10.1038/ng.273

Richard Houlston and colleagues report a genome-wide association study for lung cancer susceptibility. In addition to confirming a previous association at 15q25.1, they identify and replicate two new risk loci at 6p21.33 and 5p15.33.

Abstract - | Full Text - Common 5p15.33 and 6p21.33 variants influence lung cancer risk | PDF (484 KB) - Common 5p15.33 and 6p21.33 variants influence lung cancer risk | Supplementary information

Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin - pp1410 - 1412

Hans Christian Hennies, Uwe Kornak, Haikuo Zhang, Johannes Egerer, Xin Zhang, Wenke Seifert, Jirko Kühnisch, Birgit Budde, Marc Nätebus, Francesco Brancati, William R Wilcox, Dietmar Müller, Paige B Kaplan, Anna Rajab, Giuseppe Zampino, Valentina Fodale, Bruno Dallapiccola, William Newman, Kay Metcalfe, Jill Clayton-Smith, May Tassabehji, Beat Steinmann, Francis A Barr, Peter Nürnberg, Peter Wieacker & Stefan Mundlos

doi:10.1038/ng.252

Stefan Mundlos and colleagues report the identification of mutations in SCYL1BP1 in families with gerodermia osteodysplastica, a disorder characterized by wrinkly skin and osteoporosis. SCYL1BP1 localizes to the Golgi apparatus and interacts with Rab6.

Abstract - | Full Text - Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin | PDF (405 KB) - Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin | Supplementary information

Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing - pp1413 - 1415

Qun Pan, Ofer Shai, Leo J Lee, Brendan J Frey & Benjamin J Blencowe

doi:10.1038/ng.259

Benjamin Blencowe and colleagues report the application of next-generation sequencing technology to alternative splicing in the human genome. They detect alternative splicing events in 85% of multiexon genes, and conclude that there are approximately 100,000 such events in major human tissues.

Abstract - | Full Text - Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing | PDF (280 KB) - Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing | Supplementary information

Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines - pp1416 - 1425

John C Castle, Chaolin Zhang, Jyoti K Shah, Amit V Kulkarni, Auinash Kalsotra, Thomas A Cooper & Jason M Johnson

doi:10.1038/ng.264

Jason Johnson and colleagues present the first genome-scale compendium of human alternative splicing events in 48 tissues. These data constitute a rich resource for the study of splicing in the human genome and its impact on development, physiology and disease.

Abstract - | Full Text - Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines | PDF (1,403 KB) - Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines | Supplementary information

Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer - pp1426 - 1435

COGENT Study

doi:10.1038/ng.262

Richard Houlston and colleagues identify four new susceptibility loci for colorectal cancer through a meta-analysis of genome-wide association data, followed by replication testing in a large collection of independent samples. The study brings to ten the number of confirmed loci harboring low-penetrance risk alleles for this common malignancy.

Abstract - | Full Text - Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer | PDF (644 KB) - Meta-analysis of genome-wide association data identifies four new susceptibility loci for colorectal cancer | Supplementary information

Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation - pp1436 - 1444

Victoria Marsh, Douglas J Winton, Geraint T Williams, Nicole Dubois, Andreas Trumpp, Owen J Sansom & Alan R Clarke

doi:10.1038/ng.256

Owen Sansom and colleagues show that conditional deletion of Pten specifically from the small intestinal epithelium in mice does not disrupt normal tissue architecture, but in the context of Apc deficiency leads to rapid development of adenocarcinoma. These findings suggest that Pten does not serve a rate-limiting, intrinsic role in regulating normal intestinal stem cell physiology.

Abstract - | Full Text - Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation | PDF (1,325 KB) - Epithelial Pten is dispensable for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation | Supplementary information

Foxj1 transcription factors are master regulators of the motile ciliogenic program - pp1445 - 1453

Xianwen Yu, Chee Peng Ng, Hermann Habacher & Sudipto Roy

doi:10.1038/ng.263

Sudipto Roy and colleagues report that zebrafish homologs of the transcription factor Foxj1 are sufficient to induce the motile ciliogenic program by upregulating expression of genes encoding key components of the motile ciliary machinery. Similar findings are reported in a related study by Chris Kintner and colleagues.

Abstract - | Full Text - Foxj1 transcription factors are master regulators of the motile ciliogenic program | PDF (1,003 KB) - Foxj1 transcription factors are master regulators of the motile ciliogenic program | Supplementary information

The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos - pp1454 - 1460

Jennifer L Stubbs, Isao Oishi, Juan Carlos Izpisúa Belmonte & Chris Kintner

doi:10.1038/ng.267

Chris Kintner and colleagues report that a Xenopus homolog of the transcription factor Foxj1 is sufficient to induce motile cilia by upregulating expression of genes encoding key components of the motile ciliary machinery. Similar findings are reported in a related study by Sudipto Roy and colleagues.

Abstract - | Full Text - The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos | PDF (739 KB) - The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos | Supplementary information

Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease - pp1461 - 1465

Stefano Romeo, Julia Kozlitina, Chao Xing, Alexander Pertsemlidis, David Cox, Len A Pennacchio, Eric Boerwinkle, Jonathan C Cohen & Helen H Hobbs

doi:10.1038/ng.257

Helen Hobbs and colleagues report an association between coding variation in PNPLA3 and susceptibility to nonalcoholic fatty liver disease. The associated alleles vary in frequency among Hispanics, African Americans and European Americans and contribute to differences in disease prevalence among these ancestry groups.

First Paragraph - | Full Text - Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease | PDF (491 KB) - Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease | Supplementary information

See also: News and Views by Mohlke

Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities - pp1466 - 1471

Nicola Brunetti-Pierri, Jonathan S Berg, Fernando Scaglia, John Belmont, Carlos A Bacino, Trilochan Sahoo, Seema R Lalani, Brett Graham, Brendan Lee, Marwan Shinawi, Joseph Shen, Sung-Hae L Kang, Amber Pursley, Timothy Lotze, Gail Kennedy, Susan Lansky-Shafer, Christine Weaver, Elizabeth R Roeder, Theresa A Grebe, Georgianne L Arnold, Terry Hutchison, Tyler Reimschisel, Stephen Amato, Michael T Geragthy, Jeffrey W Innis, Ewa Obersztyn, Beata Nowakowska, Sally S Rosengren, Patricia I Bader, Dorothy K Grange, Sayed Naqvi, Adolfo D Garnica, Saunder M Bernes, Chin-To Fong, Anne Summers, W David Walters, James R Lupski, Pawel Stankiewicz, Sau Wai Cheung & Ankita Patel

doi:10.1038/ng.279

Ankita Patel and colleagues report microdeletions and microduplications on chromosome 1q21.1 in a series of individuals with features of microcephaly and macrocephaly, as well as developmental delay and neuropsychiatric abnormalities.

First Paragraph - | Full Text - Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities | PDF (543 KB) - Recurrent reciprocal 1q21.1 deletions and duplications associated with microcephaly or macrocephaly and developmental and behavioral abnormalities

See also: News and Views by O'Donovan et al.

Susceptibility loci for intracranial aneurysm in European and Japanese populations - pp1472 - 1477

Kaya Bilguvar, Katsuhito Yasuno, Mika Niemelä, Ynte M Ruigrok, Mikael von und zu Fraunberg, Cornelia M van Duijn, Leonard H van den Berg, Shrikant Mane, Christopher E Mason, Murim Choi, Emília Gaál, Yasar Bayri, Luis Kolb, Zulfikar Arlier, Sudhakar Ravuri, Antti Ronkainen, Atsushi Tajima, Aki Laakso, Akira Hata, Hidetoshi Kasuya, Timo Koivisto, Jaakko Rinne, Juha Öhman, Monique M B Breteler, Cisca Wijmenga, Matthew W State, Gabriel J E Rinkel, Juha Hernesniemi, Juha E Jääskeläinen, Aarno Palotie, Ituro Inoue, Richard P Lifton & Murat Günel

doi:10.1038/ng.240

Richard Lifton and colleagues report the identification of three susceptibility loci for intracranial aneurysm. Two of the loci are new, with SNPs on chromosome 8q likely acting through SOX17, which is required for the formation and maintenance of endothelial cells.

First Paragraph - | Full Text - Susceptibility loci for intracranial aneurysm in European and Japanese populations | PDF (462 KB) - Susceptibility loci for intracranial aneurysm in European and Japanese populations | Supplementary information

Embryonic stem cell–specific microRNAs regulate the G1-S transition and promote rapid proliferation - pp1478 - 1483

Yangming Wang, Scott Baskerville, Archana Shenoy, Joshua E Babiarz, Lauren Baehner & Robert Blelloch

doi:10.1038/ng.250

Robert Blelloch and colleagues report the use of Dgcr8 knockout embryonic stem cells to identify ES cell-specific microRNAs that regulate the G1-S transition of the ES cell cycle.

First Paragraph - | Full Text - Embryonic stem cell–specific microRNAs regulate the G1-S transition and promote rapid proliferation | PDF (522 KB) - Embryonic stem cell–specific microRNAs regulate the G1-S transition and promote rapid proliferation | Supplementary information

See also: News and Views by Kim

The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes - pp1484 - 1488

Timothy Wai, Daniella Teoli & Eric A Shoubridge

doi:10.1038/ng.258

Eric Shoubridge and colleagues report that the mitochondrial DNA genetic bottleneck occurs during postnatal ovarian folliculogenesis, when a subpopulation of mtDNAs is preferentially replicated.

First Paragraph - | Full Text - The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes | PDF (842 KB) - The mitochondrial DNA genetic bottleneck results from replication of a subpopulation of genomes | Supplementary information

Flowering-time genes modulate meristem determinacy and growth form in Arabidopsis thaliana - pp1489 - 1492

Siegbert Melzer, Frederic Lens, Jerôme Gennen, Steffen Vanneste, Antje Rohde & Tom Beeckman

doi:10.1038/ng.253

Siegbert Melzer and colleagues report that in Arabidopsis the absence of MADS box proteins SOC1 and FUL leads to phenotypes of perennial woody plants, with indeterminate meristems, secondary growth with wood formation, and recurrent growth cycles.

First Paragraph - | Full Text - Flowering-time genes modulate meristem determinacy and growth form in Arabidopsis thaliana | PDF (709 KB) - Flowering-time genes modulate meristem determinacy and growth form in Arabidopsis thaliana | Supplementary information

Regulatory activity revealed by dynamic correlations in gene expression noise - pp1493 - 1498

Mary J Dunlop, Robert Sidney Cox, III, Joseph H Levine, Richard M Murray & Michael B Elowitz

doi:10.1038/ng.281

Michael Elowitz and colleagues demonstrate that dynamic correlations in gene expression noise, as revealed using single-cell time-lapse microscopy showing time lags due to regulation, can be used to characterize active regulatory links in a synthetic and an endogenous network.

First Paragraph - | Full Text - Regulatory activity revealed by dynamic correlations in gene expression noise | PDF (846 KB) - Regulatory activity revealed by dynamic correlations in gene expression noise | Supplementary information

Molecular characterization of clonal interference during adaptive evolution in asexual populations of Saccharomyces cerevisiae - pp1499 - 1504

Katy C Kao & Gavin Sherlock

doi:10.1038/ng.280

Gavin Sherlock and colleagues report an experimental genome evolution study in Saccharomyces cerevisiae demonstrating adaptive evolution by clonal interference.

First Paragraph - | Full Text - Molecular characterization of clonal interference during adaptive evolution in asexual populations of Saccharomyces cerevisiae | PDF (400 KB) - Molecular characterization of clonal interference during adaptive evolution in asexual populations of Saccharomyces cerevisiae | Supplementary information